About

Joel D. Trinity, PhD, is an Associate Professor in the Department of Internal Medicine and an Adjunct Assistant Professor in the Department of Nutrition and Integrative Physiology at the Spencer Fox Eccles School of Medicine. He joined the Utah Veterans' Research Laboratory (UVRL) in 2009 after completing his doctoral training at The University of Texas at Austin. Dr. Trinity's research utilizes an integrative approach that combines in-vivo and in-vitro techniques to examine the impact of age and disease, specifically hypertension, on vascular function and blood flow regulation. His current research interests include the complex interactions of neural control, oxidative stress, and vascular function in populations with chronic conditions such as COPD, heart failure, and hypertension. His graduate training focused on human performance, with dissertation work studying whole body physiology, particularly peripheral and central cardiovascular performance during exercise, and how factors like core and skin temperature influence cardiovascular responses. His research also explores physiological adaptations during intense exercise and fatigue, as well as vascular and cardiovascular responses in various disease states.

Research topics

• Medicine
• Cardiology
• Internal medicine
• Virology
• Pathology

Selected publications

• Age and sex shape plasma lipid associations to skeletal muscle mitochondrial respiration and H2O2 emission

  GeroScience · 2026-01-19

  articleSenior author
  PublisherDOI

• Chamber oxygen concentration impacts mitochondrial function and hydrogen peroxide appearance in permeabilized human skeletal muscle fibers

  Biochimica et Biophysica Acta (BBA) - Bioenergetics · 2025-08-11 · 1 citations

  articleOpen access

  Skeletal muscle mitochondrial respiration is commonly assessed ex vivo using permeabilized fibers in media with high oxygen (O 2 ) concentrations to ensure that O 2 availability does not limit respiration. However, high O 2 concentrations also increase the production of reactive O 2 species that can negatively affect respiration. In this study, we tested the hypotheses that permeabilized fiber mitochondria in a high, compared to low, O 2 concentration would (i) not be different at maximal state 3 respiration rate (V max ), (ii) have lower submaximal respiration rates at submaximal O 2 concentrations, and (iii) have greater total cumulative hydrogen peroxide (H 2 O 2 ) appearance. We continuously monitored mitochondrial state 3 respiration and H 2 O 2 appearance rates using high-resolution respirometry in permeabilized skeletal muscle fibers (12 untrained participants; 22 ± 4 yrs) with either control (~127 mmHg; CON) or high (~327 mmHg; HIGH) partial pressures of O 2 (PO 2 ). V max was not different between conditions (HIGH: 80.7 ± 16.7 vs. CON: 82.3 ± 18.7 pmol/s/mg, p = 0.695). The PO 2 at 80 % V max (P 80 ) was greater in HIGH (73.9 ± 25.5 vs. 28.0 ± 7.1 mmHg, p < 0.001) and respiration rates at 5–60 mmHg PO 2 were lower for HIGH than CON (all p < 0.001). Additionally, the total cumulative H 2 O 2 appearance was greater in HIGH than CON ( n = 11; 51.5 ± 23.2 vs. 18.3 ± 10.3 pmol/mg, p < 0.001), and this difference was directly correlated with the difference in P 80 ( r = 0.655, p = 0.029). The current findings support that a high O 2 concentration, by itself, does not appear to affect V max in the permeabilized skeletal muscle fiber preparation, but the corollary increase in H 2 O 2 exposure may diminish mitochondrial state 3 respiratory function. • High O 2 concentration does not appear to affect maximal state 3 respiration in the permeabilized skeletal muscle fibers. • High O 2 concentration does increase the total cumulative appearance of H 2 O 2 during the respiration protocol. • The increase in H 2 O 2 exposure from increased O 2 levels may diminish mitochondrial state 3 respiratory function over time.

  PublisherDOI

• Differential Effects of PB125 and MitoQ Supplementation and Limb Immobilization on Mitochondrial Respiration and Protein Expression in Skeletal Muscle

  Physiology · 2025-05-01

  articleSenior author

  Mitochondrial dynamics and respiratory capacity contribute to the regulation of cellular redox state and metabolism. Disuse upregulates reactive oxygen species (ROS), disrupting physiological pathways and impairing mitochondria. This study investigated the effects of PB125 (a nuclear factor erythroid-2-like 2 [Nrf2] activator) and MitoQ (a mitochondria-targeted antioxidant) with two weeks of supplementation and two weeks of limb immobilization on mitochondrial respiration and protein expression. We hypothesized that both supplements would decrease ROS and improve mitochondrial respiration. Twenty-four participants (15F/9M, 27±7 years old) were randomly assigned to Placebo (n=8, 6F/2M), PB125 (n=9, 4F/5M), or MitoQ (n=7, 5F/2M). Skeletal muscle biopsies were taken from the vastus lateralis at baseline (V1), after 2 weeks of supplementation (V2), and after 2 weeks of limb immobilization with supplementation (V3). Mitochondrial respiration and ADP sensitivity (apparent K m ) were measured in permeabilized muscle fibers via high-resolution respirometry. Protein levels of mitochondrial complexes and mitochondrial dynamics were assessed by western blot. Skeletal muscle superoxide levels were assessed by electron paramagnetic resonance spectroscopy using mitoTEMPO-H. After 2 weeks of supplementation (V1-V2), State 3 complex I respiration (7.0±2.4 pmol/s/mg to 12.4±3.7 pmol/s/mg, p=0.030) and maximal respiration (59.1±12.5 pmol/s/mg to 73.8±14.5 pmol/s/mg, p=0.050) were enhanced with MitoQ, with no effect in PB125 or placebo (both, p&gt;0.05). There was a differential effect of supplementation on K m , where those receiving placebo had an increase in K m from V1 to V3 (237±85 to 406±194 µM ADP, p=0.032), MitoQ had a decrease from V2 to V3 (612±259 to 345±88 µM ADP, p=0.032), and there was no effect on PB125 (p&gt;0.05). From V1-V2, both PB125 and MitoQ improved only one mitochondrial protein. PB125 supplementation increased Drp1 (10.7%, p=0.031), while MitoQ supplementation increased complex I (30.0%, p=0.036). Following disuse (V2-V3), both PB125 and MitoQ saw a decrease in multiple mitochondrial proteins. PB125 had a decrease in Mfn2 (-20.0%, p=0.012), complex III (-50.7%, p=0.035), and complex V (-34.0%, p=0.046), while with MitoQ, there was a decline in PGC1α (-24.5%, p=0.035), Parkin (-10.2%, p=0.009), and complex IV (-10.7%, p=0.037). No significant changes in mitochondrial superoxide were observed for any supplementation (all, p&gt;0.05). MitoQ supplementation enhanced mitochondrial respiration, likely through complex I upregulation, however, neither PB125 nor MitoQ fully protected against reductions in mitochondrial proteins following disuse. R01HL142603VA Merit I01CX001999 This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

  PublisherDOI

• Age‐Related Changes in the Clinical Picture of Long <scp>COVID</scp>

  Journal of the American Geriatrics Society · 2025-09-01 · 2 citations

  article

  BACKGROUND: This study evaluated the impact of aging on the frequency and prevalent symptoms of Long COVID, also termed post-acute sequelae of SARS-CoV-2, using a previously developed Long COVID research index (LCRI) of 41 self-reported symptoms in which those with 12 or more points were classified as likely to have Long COVID. METHODS: We analyzed community-dwelling participants ≥ 60 years old (2662 with prior infection, 461 controls) compared to participants 18-59 years (7549 infected, 728 controls) in the Researching COVID to Enhance Recovery adult (RECOVER-Adult) cohort ≥ 135 days post-onset. RESULTS: Compared to the Age 18-39 group, the adjusted odds of LCRI ≥ 12 were higher for the Age 40-49 group (odds ratio [OR] = 1.40, 95% confidence intervals [CI] = 1.21-1.61, p < 0.001) and 50-59 group (OR = 1.31, CI = 1.14-1.51, p < 0.001), similar for the Age 60-69 group (OR = 1.09, CI = 0.93-1.27, p = 0.299), and lower for the ≥ 70 group (OR = 0.68, CI = 0.54-0.85, p < 0.001). Participants ≥ 70 years had smaller adjusted differences between infected and uninfected symptom prevalence rates than those aged 18-39 for the following symptoms: hearing loss, fatigue, pain (including joint, back, chest pain and headache), post-exertional malaise, sleep disturbance, hair loss, palpitations, and sexual desire/capacity, making these symptoms less discriminating for Long COVID in older adults than in younger. Symptom clustering, as described in Thaweethai et al. (JAMA 2023) also exhibited age-related shifts: clusters 1 (anosmia and ageusia) and 2 (gastrointestinal, chronic cough and palpitations, without anosmia, ageusia or brain fog) were more likely, and clusters 3 (brain fog, but no loss of smell or taste) and 4 (a mix of symptoms) less likely to be found in older adults (relative risk ratios for clusters 3-4 ranging from 0.10-0.34, p < 0.001 vs. 18-39 year-olds). CONCLUSIONS: Within the limits of this observational study, we conclude that in community-dwelling older adults, aging alters the prevalence and pattern of reported Long COVID.

  PublisherDOI

• Long COVID trajectories in the prospectively followed RECOVER-Adult US cohort

  Nature Communications · 2025-11-17 · 8 citations

  articleOpen access

  Longitudinal trajectories of Long COVID remain ill-defined, yet are critically needed to advance clinical trials, patient care, and public health initiatives for millions of individuals with this condition. Long COVID trajectories were determined prospectively among 3,659 participants (69% female; 99.6% Omicron era) in the National Institutes of Health Researching COVID to Enhance Recovery (RECOVER) Adult Cohort. Finite mixture modeling was used to identify distinct longitudinal profiles based on a Long COVID research index measured 3 to 15 months after infection. Eight longitudinal profiles were identified. Overall, 195 (5%) had persistently high Long COVID symptom burden, 443 (12%) had non-resolving, intermittently high symptom burden, and 526 (14%) did not meet criteria for Long COVID at 3 months but had increasing symptoms by 15 months, suggestive of distinct pathophysiologic features. At 3 months, 377 (10%) met the research index threshold for Long COVID. Of these, 175 (46%) had persistent Long COVID, 132 (35%) had moderate symptoms, and 70 (19%) appeared to recover. Identification of these Long COVID symptom trajectories is critically important for targeting enrollment for future studies of pathophysiologic mechanisms, preventive strategies, clinical trials and treatments. Long COVID has heterogeneous presentation and clinical trajectories are not well defined. Here, the authors define trajectories using data from a prospective cohort study in the United States involving symptom questionnaires from acute infection up to 15 months.

  PublisherOA PDFDOI

• Reductive stress induces unresolved ER stress and proteotoxic cardiomyopathy

  Redox Biology · 2025-06-09 · 3 citations

  articleOpen access

  Chronic reductive stress (cRS), induced by constitutive activation of Nrf2 in transgenic (TG) mouse hearts leads to pathological cardiac remodeling and diastolic dysfunction. Transcriptomic analysis revealed that both pro-reductive (PR) and reductive stress (RS) conditions disrupt ER-associated gene expression in a dose-dependent manner, with pronounced dysregulation in high-expressing TG (TGH) mice. These shifts were associated with persistent activation of the unfolded protein response (UPR), impaired ER function, and redox imbalance marked by elevated glutathione and reduced ROS levels. Proteostasis disruption under cRS led to protein misfolding, ER dilation, and aggregation of mis/unfolded proteins. TGH mice showed increased ubiquitination and accumulation of aggregated proteins, alongside inadequate proteasome activity, indicating inadequate protein quality control (PQC) mechanisms. RNA-seq data revealed transcriptional upregulation of ubiquitin-proteasome genes and downregulation of key chaperones, suggesting a failed compensatory response. Speckle-tracking echocardiography (STE) detected myocardial dyssynchrony and progressive strain abnormalities in TGH mice, correlating with increased proteotoxic burden and impaired redox homeostasis. Elevated TEI index values confirmed systolic and diastolic dysfunction. Time- and dose-dependent upregulation of Nogo/Reticulon4 transcripts and proteins further supported maladaptive cardiac remodeling. Collectively, these findings highlight that chronic RS disrupts ER homeostasis, induces proteotoxicity, and impairs cardiac structure and function, particularly in high transgene-expressing hearts.

  PublisherDOI

• Transcriptomic analyses of peripheral blood mononuclear cells reveal age-specific basal and acute exercise responsiveness differences in humans

  American Journal of Physiology-Endocrinology and Metabolism · 2025-07-23 · 3 citations

  articleOpen accessSenior authorCorresponding

  This study demonstrates that aging alters the transcriptional landscape of PBMCs at rest and in response to acute high-intensity exercise. Older adults exhibited greater transcriptomic responsiveness to exercise, particularly in pathways related to immune signaling and cellular stress. Notably, exercise elicited shared activation of NK cell-mediated processes across age groups, suggesting a conserved immunomodulatory effect. These findings provide molecular insight into how aging and exercise interact to shape immune cell function.

  PublisherDOI

• Acute sympathetic activation blunts the hyperemic and vasodilatory response to passive leg movement in young healthy males

  Physiological Reports · 2025-02-27 · 6 citations

  articleOpen accessSenior authorCorresponding

  Heightened muscle sympathetic nerve activity (MSNA) contributes to impaired vasodilatory capacity and vascular dysfunction associated with aging and cardiovascular disease. The contribution of elevated MSNA to the vasodilatory response during passive leg movement (PLM) is not fully understood. This study tested the hypothesis that elevated MSNA diminishes the vasodilatory response to PLM in healthy young males (n = 11, 25 ± 2 yr). Post exercise circulatory occlusion (PECO) following 2 min of isometric handgrip (HG) exercise performed at 25% (ExPECO 25%) and 40% (ExPECO 40%) maximum voluntary contraction was used to incrementally engage the metaboreceptors and augment MSNA. Control trials were performed without PECO (ExCON 25% and ExCON 40%) to account for changes due to HG exercise. PLM was performed 2 min after exercise and hemodynamics were assessed. MSNA was recorded by microneurography in the peroneal nerve (n = 8). Measures of MSNA (i.e., burst incidences) increased during ExPECO 25% (+15 ± 5 burst/100 bpm) and ExPECO 40% (+22 ± 4 burst/100 bpm) and returned to pre-HG levels during ExCON trials. Leg vascular conductance (vasodilation) during PLM was reduced by 16% and 44% during ExPECO 25% and ExPECO 40%, respectively. These findings indicate elevated MSNA attenuates the vasodilatory response to PLM and the magnitude of reduction in vasodilation during PLM is graded with the degree of sympathoexcitation.

  PublisherOA PDFDOI

• Acute sympathetic activation blunts the hyperemic and vasodilatory response to passive leg movement

  Research Square · 2024-05-10

  preprintOpen accessSenior author
  PublisherOA PDFDOI

• Exercise mitigates reductive stress-induced cardiac remodeling in mice

  Redox Biology · 2024-07-04 · 6 citations

  articleOpen access

  The endoplasmic reticulum (ER) regulates protein folding and maintains proteostasis in cells. We observed that the ER transcriptome is impaired during chronic reductive stress (RS) in cardiomyocytes. Here, we hypothesized that a prolonged moderate treadmill exercise mitigates the RS-induced ER dysfunction and cardiac remodeling in cardiac-specific constitutively active Nrf2 mice (CaNrf2-TG). RNA sequencing showed notable alterations in the ER transcriptome of TG hearts at 4, 12, and 24 weeks (16, 28, and 35 genes, respectively). Notably, the downregulation of ER genes was significant at 12 weeks, and further pronounced at 24 weeks, at which the cardiac pathology is evident. We also observed increased levels of ubiquitinated proteins in CaNrf2-TG hearts across all ages, along with VCP, a marker of ERAD function, at 24 weeks. These findings indicate that constitutive Nrf2 activation and RS impair protein-folding activity and augments ERAD function over time. Exercise intervention for 20 weeks (beginning at 6 weeks of age), reduced cardiomyocyte hypertrophy (from 448 μm2 to 280 μm2) in TG mice, through adaptive remodeling, and preserved the cardiac function. However, while exercise did not influence antioxidants or ER stress protein levels, it significantly improved ERAD function and autophagy flux (LC-I to LC-II) in the TG-EXE hearts. Collectively, our findings underscore the prophylactic potential of exercise in mitigating RS-associated pathology, highlighting its essential role in maintaining cellular proteostasis through ER-independent mechanisms.

  PublisherDOI

Recent grants

• Understanding the Exercise-Hypertension Paradox: Implication for Rehabilitation

  NIH · 2014–2019

• Targeting Oxidative Stress to Prevent Vascular and Skeletal Muscle Dysfunction during Disuse

  NIH · $2.9M · 2019–2026

• Targeting Oxidative Stress to Prevent Vascular and Skeletal Muscle Dysfunction during Disuse

  NIH · 2019–2023

Frequent coauthors

• Russell S. Richardson

  University of Utah

  474 shared

• Gwenaël Layec

  187 shared

• D. Walter Wray

  University of Utah

  134 shared

• Jayson R. Gifford

  127 shared

• Stephen J. Ives

  Skidmore College

  120 shared

• Corey R. Hart

  Mayo Clinic

  115 shared

• Ryan M. Broxterman

  University of Utah

  113 shared

• Melissa A. H. Witman

  University of Delaware

  92 shared

Labs

• UVRL (University of Utah Vascular Research Laboratory)PI

Education

• Ph.D.

  The University of Texas at Austin